The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized double-blind study

Abstract

Objective: To determine if the combination of lifestyle (caloric restriction and exercise) and metformin (MET) would be superior to lifestyle and placebo (PBO) in improving the polycystic ovary syndrome (PCOS) phenotype.

Design: Double-blind randomized 6-month trial of MET versus PBO.

Setting: Two academic medical centers.

Patient(s): One hundred fourteen subjects with PCOS were randomized to MET (N = 55) or PBO (N = 59).

Intervention(s): Subjects collected urine daily for ovulation monitoring, had monthly monitoring of hormones and weight and determination of body composition by dual-energy x-ray absorptiometry, glucose tolerance, and were evaluated for quality of life at baseline and completion.

Main outcome measure(s): Ovulation rates and testosterone levels.

Result(s): Dropout rates were high. There was no significant difference in ovulation rates. Testosterone levels were significantly lower compared with baseline in the MET group at 3 mos but not at 6 mos. There were no differences in weight loss between groups, but MET showed a significant decline at 6 months compared with baseline (-3.4 kg, 95% confidence interval -5.3 to -1.5 kg). We noted divergent effects of MET versus PBO on oral glucose tolerance test indices of insulin sensitivity (increased) and secretion (worsened). Total bone mineral density increased significantly in MET. There were no differences in quality of life measures between the groups. The MET group had increased diarrhea and headache, but fewer bladder infections and musculoskeletal complaints.

Conclusion(s): The addition of metformin to lifestyle therapy produced little reproductive or glycemic benefit in women with PCOS, although our study had limited power owing to a high dropout rate. It is not possible at baseline to identify women likely to drop out.

Trial registration: ClinicalTrials.gov NCT00151411.

Figure 1

Flow Chart of Study Participants

Figure 2

Primary Outcome A Frequency of the number of ovulations by Urinary PdG per treatment arm. There was no difference between groups. This model adjusted for the covariates of prior metformin use, center, baseline age, and baseline body mass index in addition to use of the logarithm of the number of days on the trial as on offset to help account for subject dropout. Secondary Outcomes B. Change in testosterone levels at baseline, 3 mos and study completion at 6 mos per treatment arm. C. Change in weight (kg) by month per treatment arm. * P < 0. 05 for the change from baseline within the metformin group.